Results from a study spearhead by researchers at the Vall d´Hebron Institute of Oncology (VHIO) in Barcelona, Spain, show that the blockade of the multi-functional cytokine LIF (image)induces tumor-infiltrating T Cells to home in on and eliminate cancer. Reported on June 11, 2019 in Nature Communications, this research was led by corresponding and co-first author Joan Seoane, PhD, Co-Program Director of Preclinical and Translational Research at VHIO, and ICREA Research Professor, and has now culminated in a Phase I clinical trial currently assessing the safety and efficacy of LIF (leukemi inhibitory factor) inhibitors in patients across three sites: the Vall d'Hebron University Hospital (HUVH), Memorial Sloan Kettering Cancer Center (MSKCC - New York, USA), and the Princess Margaret Cancer Center (Toronto, Canada). The open-access article is titled “LIF Regulates CXCL9 In Tumor-Associated Macrophages and Prevents CD8+ T Cell Tumor-Infiltration Impairing Anti-PD1 Therapy.” Developed by VHIO, the novel agent MSC-1 inhibits LIF and has now been shown to have a dual mechanism of action. First, in tumors expressing high levels of LIF, the protein LIF promotes the proliferation of cancer stem cells. LIF blockade eliminates these tumor-initiating stem cells, putting the brakes on metastatic cell spread and cancer recurrence. Additionally, elevated LIF expression disables the anti-tumor alarm system and stops the immune system from thwarting cancer's plans. Blocking LIF reactivates the alarm to call an anti-tumoral immune response.
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